Localization of factor VIII-procoagulant antigen: an immunohistological survey of the human body using monoclonal antibodies

Various organs, including liver, spleen, heart, lung, kidney, intestines, lymph nodes, pancreas, bone marrow, and thymus, were investigated for the presence of factor VIII-procoagulant antigen (VIIICAg) and factor VIII-related antigen (VIIIRAg), using a panel of monoclonal antibodies directed to factor VIII-von Willebrand factor in combination with a sensitive immunoperoxidase staining technique. In addition to hepatic sinusoidal endothelial cells, the presence of VIIICAg was demonstrated in mononuclear cells sporadically present in lymph nodes, in the alveolar septa of lung, and in the red pulp of spleen. The identity of these mononuclear cells could not be unequivocally determined. Based on morphological criteria, however, it is tentatively concluded that these cells are nonlymphoid and belong to the mononuclear phagocyte system. The presence of VIII-RAg was confined to vascular endothelial cells, hepatic sinusoidal endothelial cells, cells lining the venous sinuses of the red pulp of the spleen, cells lining renal glomeruli and lung capillaries, platelets, and megakaryocytes.     

Characterization of 25 monoclonal antibodies to factor VIII-von Willebrand factor: relationship between ristocetin-induced platelet aggregation and platelet adherence to subendothelium

We have studied the role of factor VIII-von Willebrand factor (FVIII- vWF) in both platelet adherence to subendothelium and ristocetin- induced platelet aggregation using monoclonal antibodies to human FVIII- vWF. Twenty-five monoclonal antibodies were obtained, two of which were directed to the factor VIII moiety of FVIII-vWF; one of these two completely inhibited the procoagulant activity (FVIII:C). The remaining 23 monoclonal antibodies were directed to the von Willebrand factor moiety of FVIII-vWF. The ability of the latter monoclonal antibodies to inhibit platelet adherence to arterial subendothelium was investigated with a perfusion model. According to the number of platelets adhering to the subendothelium, three groups of monoclonal antibodies could be discerned: (A) antibodies not affecting platelet adherence; (B) antibodies that inhibited platelet adherence to the level as observed when von Willebrand's disease plasma was tested; and (C) antibodies that completely inhibited both platelet adherence to subendothelium and ristocetin-induced platelet aggregation. The two antibodies present in group C competed for the same or closely related epitope(s) present on FVIII-vWF. These results demonstrate that a domain is present on the FVIII-vWF molecule that is associated both with ristocetin-induced aggregation and with the ability of FVIII-vWF to support platelet adherence to the subendothelium. Based on these observations, it is concluded that ristocetin-induced binding of FVIII-vWF to platelets reflects, at least in part, a physiologic mechanism regulating the function of FVIII-vWF in primary hemostasis.     

The validation and translation of Multidimensional Measure of Informed Choice in Greek

Objective

to translate the original English version of the Multidimensional Measure of Informed Choice (MMIC) into Greek, to adapt it culturally to Greece, and to determine its psychometric properties for the assessment of informed choice in antenatal screening for Down syndrome.

Design

survey using self-administrated questionnaires.

Setting

public hospital in Athens, Greece.

Participants

135 pregnant women with gestational age between 11th and 20th week just prior to having antenatal screening for Down syndrome.

Findings

96% of women had a positive attitude towards screening and 45% had a good level of knowledge concerning the screening process for Down syndrome. Using a standard measure of informed choice, validated for use in Greek, it was found that 44% of women made an informed choice, and thus 56% of women made an uninformed choice. The internal consistency of the scales was good; Cronbach's alpha was found to be 0.76 for the attitude scale and 0.64 for the knowledge scale, suggesting that all items were appropriate to measure. The performed factor analysis of the attitude scale indicated three factors with an eigenvalue over 1.0. Those factors were responsible for 87% of the variance.

Key conclusions

this study indicates that the Greek version of the MMIC appears to be a reliable and valid tool for measuring informed choice in antenatal screening for Down syndrome. Due to its short length and consumption of time, it seems to be a practical instrument for use in Greek antenatal clinics.     

Volunteering on Heritage at Risk sites and wellbeing: A qualitative interview study

Introduction

We explored experiences of volunteering in Heritage at Risk (HAR) projects, intended to mitigate the deterioration to historic assets, and the relationship with wellbeing. We aimed to understand the value of HAR to volunteers' wellbeing and relationships between HAR programme characteristics such as location, asset type and type of activity.

Methods

We used a qualitative design with semi-structured interviews of a purposive sample of volunteers recruited via Historic England (HE), employing Systematic Grounded Theory involving open, axial and selective coding.

Findings

We interviewed 35 volunteers (18 male and 17 female) participating in 10 HAR projects. We identified six themes from the data analysis. (1) Purpose—was associated with volunteering motivations; there were some barriers to volunteering and many types of facilitators, including accessibility to local heritage sites. (2) Being—volunteers showed an appreciation and attachment to their place of residence. (3) Capacity—to learn heritage-specific skills and diversify experiences in learning new skills (life, technical and personal). (4) Sharing—community engagement, connectedness, and inclusivity captured diversity and inclusion within volunteers across age, ethnicity, ability, and gender. (5) Self-nurture—HAR volunteering created physical, psychological, and social benefits with limited risks and adverse outcomes. (6) Self-actualisation—described volunteers reflecting on their experiences.

Conclusion

HAR volunteering was associated with positive physical, social and psychological wellbeing outcomes. The study provides an evidence base for specific wellbeing benefits of volunteering at Heritage at Risk sites, although we could not conclude that HAR project activity was the cause of increased wellbeing.

Public Contribution

Staff from HE were involved in designing the project brief. In selecting the HAR project sites, we took advice and recommendations from HE staff across all their six regional offices.